Abstract
Endothelin-1 (ET-1) is associated with endothelial dysfunction and vasoconstriction. Increased circulating ET-1 levels are associated with long-term cardiovascular mortality. Renalase, released from kidney, metabolizes catecholamines and regulates blood pressure. An increase in circulating renalase levels has been reported in patients with chronic kidney disease (CKD) and is associated with coronary artery disease (CAD). We hypothesized the existence of a synergistic effect of serum renalase levels and CKD on ET-1 levels in patients with CAD. We evaluated 342 non-diabetic patients with established CAD. ET-1 and renalase levels were measured in all patients after an overnight fast. Patients with CKD had higher ET-1 (1.95 ± 0.77 vs. 1.62 ± 0.76 pg/ml, P < 0.001) and renalase levels (46.8 ± 17.1 vs. 33.9 ± 9.9 ng/ml, P < 0.001) than patients without CKD. Patients with both CKD and high renalase levels (>the median of 36.2 ng/ml) exhibited the highest serum ET-1 (P value for the trend <0.001). According to multivariate linear regression analysis, the combination of high serum renalase levels with CKD was a significant risk factor for increased serum ET-1 levels (regression coefficient = 0.297, 95% confidence interval = 0.063‒0.531, P = 0.013). In conclusion, our data suggest a synergistic effect of high serum renalase levels and CKD on increases in ET-1 levels in patients with established CAD.
Highlights
Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD)[1]
Of the total of 342 patients with established coronary artery disease (CAD), 85 with an estimated glomerular filtration rate (eGFR)
We found that either elevated serum renalase or low eGFR was associated with elevated serum ET-1 levels
Summary
Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD)[1]. The progression of CVD and CKD are tightly linked, by sharing common risk factors and by multi-system crosstalk between the kidney and the heart[2,3]. Many patients progress to end-stage renal disease (ESRD) and die of CVD7. This suggests that RAAS blockade alone is not sufficient to prevent complications of CKD. Endothelin-1 (ET-1) is a potent vasoconstrictor[8] It is produced by the endothelium and acts on vascular smooth muscle[9]. A flavin adenine dinucleotide-dependent amine oxidase produced by the kidney, metabolizes catecholamines and may be a therapeutic target for the management of the overstimulated sympathetic system[15]. It has been hypothesized that circulating renalase may be a risk factor for CVD21,22. Since the mechanistic bridge between CKD and CAD has yet to be elucidated, we investigated the effect of renalase and CKD on ET-1 levels in patients with established CAD
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